Thapsigargin

Thapsigargin

Thapsigargin is a naturally occurring sesquiterpene lactone derived from the plant Thapsia garganica. It is a potent inhibitor of the Sarco/Endoplasmic Reticulum Ca2+ ATPase (SERCA), a calcium pump located in the sarcoplasmic and endoplasmic reticulum of cells. Thapsigargin has been extensively used in biological research to increase intracellular calcium concentrations.

History

Thapsigargin was first isolated from the plant Thapsia garganica in the 1970s. The plant, also known as deadly carrot, has been used in traditional medicine for centuries. The name "thapsigargin" is derived from the genus name Thapsia and the Greek word "gargan", meaning quick-acting, which refers to the plant's potent toxic effects.

Mechanism of Action

Thapsigargin inhibits the SERCA pump by binding to a specific site on the pump, preventing the reuptake of calcium ions into the sarcoplasmic and endoplasmic reticulum. This leads to an increase in the concentration of calcium ions in the cytosol, which can trigger a variety of cellular responses, including cell death.

Applications in Research

Thapsigargin has been used in a wide range of biological research, particularly in studies investigating the role of calcium in cell signaling. It has also been used to study the function of the SERCA pump and the effects of increased intracellular calcium concentrations on cell function and survival.

Potential Therapeutic Uses

Thapsigargin has potential therapeutic uses in the treatment of certain types of cancer. It has been shown to induce apoptosis, or programmed cell death, in cancer cells. Researchers are currently investigating the use of thapsigargin as a prodrug in targeted cancer therapy.

Safety and Toxicity

Thapsigargin is highly toxic and must be handled with care. It can cause skin and eye irritation, and if ingested or inhaled, it can cause severe health effects.

See Also

• Sarco/Endoplasmic Reticulum Ca2+ ATPase
• Calcium signaling
• Apoptosis
• Prodrug